Successful invasive plant eradication is rare, because the methods used target the adult stage, not taking into account the development capacity of a large seedbank. Heating by microwave was considered, because it offers a means to quickly reach the temperature required for loss of seed viability and inhibition of germination. Previous results were not encouraging, because homogeneous and deep-wave penetration was not achieved, and the various parameters that can affect treatment effectiveness were incompletely addressed. This study aimed to determine, under experimental conditions, the best microwave treatment to inhibit invasive species seed germination in terms of power (2, 4, 6 kW) and duration (2, 4, 8 min) of treatments and depending on soil moisture (10%, 13%, 20%, 30%) and seed burial depth (2, 12 cm). Three invasive species were tested: Bohemian knotweed, giant goldenrod, and jimsonweed. The most effective treatments required relatively high power and duration (2kW8min, 4kW4min, 6kW2min, and 6kW4min; 4kW8min and 6kW8min were not tested for technical reasons), and their effectiveness diminished with increasing soil moisture with germination percentage between 0% and 2% for the lowest soil moisture, 0% and 56% for intermediate soil moisture, and 27% and 68% in control treatments. For the highest soil moisture, only 2kW8min and 4kW4min reduced germination percentage between 2% and 19%. Occasionally, germination of seeds located at the 12-cm depth was more strongly affected. Giant goldenrod seeds were the most sensitive, probably due to their small size. Results are promising and justify further experiments before developing a field microwave device to treat large volumes of soil infested by invasive seed efficiently and with reasonable energy requirements. Other types of soil, in terms of texture and organic matter content, should be tested in future experiments, because these factors influence soil water content and, consequently, microwave heating.